This Article Full Text Full Text (PDF) All Versions of this Article: 98/1/105    most recent 01.RES.0000197851.11031.9cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Moosmang, S. Articles by Hofmann, F. Search for Related Content PubMed PubMed Citation Articles by Moosmang, S. Articles by Hofmann, F. Related Collections Animal models of human disease Other hypertension Genetically altered mice Hypertension - basic studies Ion channels/membrane transport Genetics of cardiovascular disease Other Vascular biology

(Circulation Research. 2006;98:105.)
© 2006 American Heart Association, Inc.

Cellular Biology

Antihypertensive Effects of the Putative T-Type Calcium Channel Antagonist Mibefradil Are Mediated by the L-Type Calcium Channel Ca_v1.2

Sven Moosmang, Nicole Haider, Birgit Brüderl, Andrea Welling, Franz Hofmann

From the Institut für Pharmakologie und Toxikologie, Technische Universität München, Germany.

Correspondence to Dr Sven Moosmang, Institut für Pharmakologie und Toxikologie der Technischen Universität München, Biedersteiner Strasse 29, 80802 München, Germany. E-mail moosmang{at}ipt.med.tu-muenchen.de

The role of T-type Ca²⁺ channels for cardiovascular physiology, in particular blood pressure regulation, is controversial. Selective blockade of T-type Ca²⁺ channels in resistance arteries has been proposed to explain the effect of the antihypertensive drug mibefradil. In the present study, we used a third generation, time- and tissue-specific conditional knockout model of the L-type Ca²⁺ channel Ca_v1.2 (Ca_v1.2^SMAKO mice) to genetically dissect the effects of mibefradil on T- and L-type Ca²⁺ channels. Myogenic tone and phenylephrine-induced contraction in hindlimb perfusion experiments were sensitive to mibefradil in control mice, whereas the drug showed no effect in Ca_v1.2-deficient animals. Mean arterial blood pressure in awake, freely moving control mice was reduced by 38±2.5 mm Hg at a dose of 1.25 mg/kg bodyweight mibefradil, but not changed in Ca_v1.2^SMAKO mice. These results demonstrate that the effect of the putative T-type Ca²⁺ channel-selective blocker mibefradil on blood pressure and small vessel myogenic tone is mediated by the Ca_v1.2 L-type Ca²⁺ channel.

Key Words: calcium channel • T-type • L-type • mibefradil • blood pressure

This article has been cited by other articles:

				C. J. Ball, D. P. Wilson, S. P. Turner, D. A. Saint, and J. F. Beltrame Heterogeneity of L- and T-Channels in the Vasculature: Rationale for the Efficacy of Combined L- and T-Blockade Hypertension, April 1, 2009; 53(4): 654 - 660. [Abstract] [Full Text] [PDF]

				E. Perez-Reyes, A. L. Van Deusen, and I. Vitko Molecular Pharmacology of Human Cav3.2 T-Type Ca2+ Channels: Block by Antihypertensives, Antiarrhythmics, and Their Analogs J. Pharmacol. Exp. Ther., February 1, 2009; 328(2): 621 - 627. [Abstract] [Full Text] [PDF]

				R. Schubert, D. Lidington, and S.-S. Bolz The emerging role of Ca2+ sensitivity regulation in promoting myogenic vasoconstriction Cardiovasc Res, January 1, 2008; 77(1): 8 - 18. [Abstract] [Full Text] [PDF]

				K. R. Watterson, K. M. Berg, D. Kapitonov, S. G. Payne, A. S. Miner, R. Bittman, S. Milstien, P. H. Ratz, and S. Spiegel Sphingosine-1-phosphate and the immunosuppressant, FTY720-phosphate, regulate detrusor muscle tone FASEB J, September 1, 2007; 21(11): 2818 - 2828. [Abstract] [Full Text] [PDF]

				X. F. Figueroa, C.-C. Chen, K. P. Campbell, D. N. Damon, K. H. Day, S. Ramos, and B. R. Duling Are voltage-dependent ion channels involved in the endothelial cell control of vasomotor tone? Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1371 - H1383. [Abstract] [Full Text] [PDF]

				L. Lipskaia, C. Pinet, Y. Fromes, S. Hatem, I. Cantaloube, A. Coulombe, and A.-M. Lompre Mutation of {delta}-Sarcoglycan Is Associated with Ca2+-Dependent Vascular Remodeling in the Syrian Hamster Am. J. Pathol., July 1, 2007; 171(1): 162 - 171. [Abstract] [Full Text] [PDF]

				A. M. Blanks, Z.-H. Zhao, A. Shmygol, G. Bru-Mercier, S. Astle, and S. Thornton Characterization of the molecular and electrophysiological properties of the T-type calcium channel in human myometrium J. Physiol., June 15, 2007; 581(3): 915 - 926. [Abstract] [Full Text] [PDF]

				K. Hayashi, S. Wakino, N. Sugano, Y. Ozawa, K. Homma, and T. Saruta Ca2+ Channel Subtypes and Pharmacology in the Kidney Circ. Res., February 16, 2007; 100(3): 342 - 353. [Abstract] [Full Text] [PDF]

				B. S. Freeze, M. M. McNulty, and D. A. Hanck State-Dependent Verapamil Block of the Cloned Human Cav3.1 T-Type Ca2+ Channel Mol. Pharmacol., August 1, 2006; 70(2): 718 - 726. [Abstract] [Full Text] [PDF]